Metformin administration modulates neurosteroids secretion in non-obese amenorrhoic patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is observed frequently to be related to increased insulin resistance. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality and the restoration of normal ovarian function. Metformin administration reduces insulin resistance and androgen production both from the ovary and adrenal gland. AIM: On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg per os twice daily) to better understand what changes might be induced by metformin on adrenal and ovarian function and in terms of temporal coupling of the pulsatile profiles of luteinizing hormone (LH), cortisol and allopregnanolone, the latter representative of the neurosteroid family. METHOD: A group of non-obese PCOS patients (n = 8) was enrolled after informed consent and underwent to a pulsatility study for LH, cortisol and allopregnanolone, and an oral glucose tolerance test before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment. RESULTS: Plasma androgen levels were decreased significantly by metformin treatment, as were plasma LH and allopregnanolone levels and insulin resistance. Metformin administration decreased LH pulse amplitude but not pulse frequency. On the contrary, cortisol and allopregnanolone showed a significant change in pulse frequency. When temporal coupling was tested between pulsatile profiles of LH or cortisol with allopregnanolone, cortisol pulses were temporally coupled to allopreganolone peaks both before and under metformin administration while LH pulses were temporally coupled to allopreganolone secretory peaks only under metformin treatment. CONCLUSIONS: Our data demonstrate that metformin administration modulates LH secretion as well as cortisol and allopregnanolone pulsatile release. In addition, the results demonstrate that adrenal and ovarian steroidogenic activity is greatly modulated by any change in insulin sensitivity.